Major depression is a neuropsychiatric illness characterized by a persistently low mood or diminished interests in one's surroundings, accompanied by at least several of the following symptoms: Reduced energy and motivation, difficulty concentrating, altered sleep and appetite, and at times, suicidal ideation (American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, ed. 4. Washington, American Psychiatric Association, 1994). Major depression without a history of abnormally elevated mood and energy (mania) is termed “unipolar major depression.” However, a sizeable proportion of depressed patients presenting for treatment have bipolar disorder (also known as manic depressive illness), where there is a history of mania, or a milder form of mood elevation known as hypomania (Goodwin F K, Jamison K R: Manic Depressive Illness. London, Oxford University Press, 1990). Whether part of a unipolar or a bipolar illness, major depression is associated with high rates of morbidity and mortality, with suicide rates of 10-25% (Kaplan H I, Sadock B J (eds): Synopsis of Psychiatry. Baltimore, Williams & Wilkins, 1998, p. 866). According to the World Health Organization (WHO), major depression is the fourth leading cause of vocational disability on earth (Murray C J L, Lopez A D (eds): The Global Burden of Disease. Geneva, World Health Organization, 1996, vol. 1). Furthermore, the incidence of major depression increased and the age of onset of depression decreased with each passing decade of the 20th century (Klerman G L, Weissman M M: Increasing rates of depression. JAMA 1989; 261:2229-2235). Effective psychotherapeutic and pharmacological antidepressant treatments for major depression exist, but each has shortcomings. Two modern forms of psychotherapy, cognitive-behavioral therapy and interpersonal therapy, have shown efficacy in controlled studies of major depression (Kaplan, 1998, pp. 885-931). However, for moderate or severe depression, antidepressant medication is generally more effective, rapidly acting, and less expensive than psychotherapy. The combination of psychotherapy and medications has recently been shown to be superior to either treatment modality (Keller M B, et al.: A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression. N Engl J Med 2000; 342:1462-1470). There are more than 20 approved antidepressant drugs available in the United States. All of these medications have proven acute efficacy for major depression. The newer agents, such as the selective serotonin reuptake inhibitors (SSRIs), are far less toxic than the older classes of antidepressants, but even the SSRIs carry a substantial burden of side-effects, including sexual dysfunction, sleep disturbance, and weight gain (Kaplan, 1998). In addition, no currently available antidepressant is acutely effective in more than 60-70% of the patients who receive it. Furthermore, long-term data exists for only a few antidepressant drugs, and it appears that efficacy may diminish over time with some agents (Fredman S J, et al.: Partial response, nonresponse, and relapse with selective serotonin reuptake inhibitors in major depression: a survey of current “next-step” practices. J Clin Psychiatry; 2000, 61:403-408). Thus, there is a need for newer treatments, with greater efficacy and safety, as well as fewer side-effects.